PDLIM4

Summary

PDLIM4 (PDZ and LIM domain 4, HGNC:16501) is a protein-coding gene on chromosome 5q31.1, encoding PDZ and LIM domain protein 4 (P50479). Suppresses SRC activation by recognizing and binding to active SRC and facilitating PTPN13-mediated dephosphorylation of SRC ‘Tyr-419’ leading to its inactivation.

Enables alpha-actinin binding activity; protein homodimerization activity; and protein phosphatase binding activity. Involved in actin cytoskeleton organization. Located in several cellular components, including lamellipodium; perinuclear region of cytoplasm; and stress fiber. Part of filamentous actin. Implicated in osteoporosis.

Source: NCBI Gene 8572 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 45 total
• Phenotypes (HPO): 2
• MANE Select transcript: NM_003687

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16501
Approved symbol	PDLIM4
Name	PDZ and LIM domain 4
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	RIL
Ensembl gene	ENSG00000131435
Ensembl biotype	protein_coding
OMIM	603422
Entrez	8572

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000253754, ENST00000379018, ENST00000418373, ENST00000462597, ENST00000463615, ENST00000474421, ENST00000484620, ENST00000889983, ENST00000889984, ENST00000889985, ENST00000889986, ENST00000924881, ENST00000947542, ENST00000947543

RefSeq mRNA: 2 — MANE Select: NM_003687 NM_001131027, NM_003687

CCDS: CCDS4152, CCDS47261

Canonical transcript exons

ENST00000253754 — 7 exons

Exon	Start	End
ENSE00000899290	132266464	132266545
ENSE00000899296	132271791	132271908
ENSE00001042731	132257696	132257827
ENSE00001909392	132272025	132273454
ENSE00003464900	132262609	132262760
ENSE00003483077	132271303	132271466
ENSE00003555254	132270915	132271093

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 97.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.6860 / max 292.4461, expressed in 1432 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58431	27.8160	1420
58430	8.1732	1345
58432	0.6968	377

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus muscularis layer	UBERON:0035833	97.84	gold quality
lower esophagus	UBERON:0013473	97.83	gold quality
left uterine tube	UBERON:0001303	97.76	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.47	gold quality
body of uterus	UBERON:0009853	97.37	gold quality
tibial nerve	UBERON:0001323	97.22	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.06	gold quality
cartilage tissue	UBERON:0002418	96.96	gold quality
skin of leg	UBERON:0001511	96.95	gold quality
mucosa of stomach	UBERON:0001199	96.68	gold quality
lower esophagus mucosa	UBERON:0035834	96.60	gold quality
skin of abdomen	UBERON:0001416	96.32	gold quality
ascending aorta	UBERON:0001496	96.02	gold quality
thoracic aorta	UBERON:0001515	95.90	gold quality
cervix squamous epithelium	UBERON:0006922	95.87	silver quality
descending thoracic aorta	UBERON:0002345	95.83	gold quality
minor salivary gland	UBERON:0001830	95.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.76	gold quality
esophagus	UBERON:0001043	95.71	gold quality
aorta	UBERON:0000947	95.65	gold quality
tibial artery	UBERON:0007610	95.62	gold quality
popliteal artery	UBERON:0002250	95.61	gold quality
pancreatic ductal cell	CL:0002079	95.53	gold quality
stromal cell of endometrium	CL:0002255	95.44	gold quality
mouth mucosa	UBERON:0003729	95.27	gold quality
zone of skin	UBERON:0000014	95.15	gold quality
artery	UBERON:0001637	94.85	gold quality
right atrium auricular region	UBERON:0006631	94.65	gold quality
ectocervix	UBERON:0012249	94.65	gold quality
endocervix	UBERON:0000458	94.36	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	44.26
E-MTAB-8410	yes	32.34
E-MTAB-6678	yes	26.65
E-HCAD-1	yes	25.81
E-CURD-114	yes	22.08
E-HCAD-11	yes	21.16
E-ANND-3	yes	11.53
E-GEOD-125970	yes	9.08
E-MTAB-5061	yes	8.90
E-ENAD-27	yes	4.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting PDLIM4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-1272	99.34	68.79	878
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-6873-5P	98.45	66.14	1417

Literature-anchored findings (GeneRIF, showing 12)

• RIL and its variant sequences may be an important determinant of osteoporosis (PMID:12908099)
• Ril modulates actin stress fiber turnover and enhances the association with actinin and actins. (PMID:14729062)
• Results showed that the hypermethylation of PDLIM4 gene could be used as a sensitive molecular tool in detection of prostate. (PMID:16489065)
• RIL methylation is a marker of adverse prognosis independent of chromosome 5 and 7 deletions. (PMID:17332327)
• several genes that are known to be regulated by DNA methylation were up-regulated dramatically by integrin alpha6beta4 expression, including S100A4, FST, PDLIM4, CAPG, and Nkx2.2. (PMID:19011242)
• PDLIM4 may function as a tumor suppressor, involved in the control of cell proliferation by associating with actin in prostate cancer cells. (PMID:19212833)
• Reversion-induced LIM interaction with Src reveals a novel Src inactivation cycle. (PMID:19307596)
• Actin cytoskeleton remodeling by the alternatively spliced isoform of PDLIM4/RIL protein. (PMID:21636573)
• Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancers was associated with clinical characteristics, but only RASSF1A methylation was associated with time to first recurrence and overall survival. (PMID:22695491)
• The levels of the EDNRB, HJURP and p60/CAF-1 proteins were strongly associated with overall survival in high-grade gliomas patients (p<0.001, p<0.001 and p=0.002, respectively), whereas the one of PDLI4 was not (P=0.11). (PMID:24039914)
• Our study provides supportive evidence for the contribution of PDLIM4 gene polymorphisms to the susceptibility to osteoporotic fracture and suggests that rs270611 and rs3900945 are genetic risk factors, while rs366512 might be a genetic protective factor against osteoporotic fracture in elderly Han individuals. (PMID:30578378)
• Low expression of PDLIM4 is associated with growth and invasion of ovarian cancer. (PMID:31376371)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdlim4	ENSDARG00000068973
mus_musculus	Pdlim4	ENSMUSG00000020388
rattus_norvegicus	Pdlim4	ENSRNOG00000050794

Paralogs (7): PDLIM1 (ENSG00000107438), PDLIM2 (ENSG00000120913), LDB3 (ENSG00000122367), PDLIM3 (ENSG00000154553), PDLIM5 (ENSG00000163110), PDLIM7 (ENSG00000196923), PRICKLE4 (ENSG00000278224)

Protein

Protein identifiers

PDZ and LIM domain protein 4 — P50479 (reviewed: P50479)

Alternative names: LIM protein RIL, Reversion-induced LIM protein

All UniProt accessions (3): A0A0S2Z4N4, C9J542, P50479

UniProt curated annotations — full annotation on UniProt →

Function. Suppresses SRC activation by recognizing and binding to active SRC and facilitating PTPN13-mediated dephosphorylation of SRC ‘Tyr-419’ leading to its inactivation. Inactivated SRC dissociates from this protein allowing the initiation of a new SRC inactivation cycle. Involved in reorganization of the actin cytoskeleton. In nonmuscle cells, binds to ACTN1 (alpha-actinin-1), increases the affinity of ACTN1 to F-actin (filamentous actin), and promotes formation of actin stress fibers. Involved in regulation of the synaptic AMPA receptor transport in dendritic spines of hippocampal pyramidal neurons directing the receptors toward an insertion at the postsynaptic membrane. Links endosomal surface-internalized GRIA1-containing AMPA receptors to the alpha-actinin/actin cytoskeleton. Increases AMPA receptor-mediated excitatory postsynaptic currents in neurons. Involved in reorganization of the actin cytoskeleton and in regulation of cell migration. In response to oxidative stress, binds to NQO1, which stabilizes it and protects it from ubiquitin-independent degradation by the core 20S proteasome. Stabilized protein is able to heterodimerize with isoform 1 changing the subcellular location of it from cytoskeleton and nuclei to cytosol, leading to loss of isoforms 1 ability to induce formation of actin stress fibers. Counteracts the effects produced by isoform 1 on organization of actin cytoskeleton and cell motility to fine-tune actin cytoskeleton rearrangement and to attenuate cell migration.

Subunit / interactions. Homodimer. Interacts with PTPN13. Interacts (via C-terminus only or via combined C-terminus and LIM domain, but not LIM domain only) with PTPN13 (via the second or fourth PDZ domains). Found in a complex with PTPN13 and TRIP6. Interacts (via PDZ domain) with ACTN1 and ACTN2 (via C-terminal SDL residues). Interacts (via PDZ domain) with TRIP6 (via the second LIM domain or via the third LIM domain plus C-terminus). Interacts (via LIM domain) with GRIA1 (via C-terminus); this interaction as well as the interaction with alpha-actinin is required for their colocalization in early endosomes. Interacts with PDLIM1. Forms (via LIM domain) a heterodimer with PDLIM3. Interacts directly with SRC (via kinase domain and to a lesser extent the SH2 domain). Isoform 2 interacts with NQO1. NQO1-stabilized isoform 2 heterodimerizes with isoform 1.

Subcellular location. Cytoplasm. Cytoskeleton. Nucleus. Perinuclear region. Cell projection. Lamellipodium. Dendritic spine. Early endosome membrane. Recycling endosome membrane. Synapse. Synaptosome Cytoplasm.

Tissue specificity. Found in brain.

Post-translational modifications. Phosphorylated on tyrosine residue(s). Can be dephosphorylated by PTPN13.

Induction. Expression is up-regulated by UV irradiation and to a lesser extent by oxidative stress.

Polymorphism. Genetic variations in PDLIM4 may be correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture. Osteoporosis is characterized by reduced bone mineral density, disruption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.

Isoforms (2)

UniProt ID	Names	Canonical?
P50479-1	1	yes
P50479-2	2

RefSeq proteins (2): NP_001124499, NP_003678* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR001781	Znf_LIM	Domain
IPR031847	PDLI1-4/Zasp-like_mid	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR050604	PDZ-LIM_domain	Family

Pfam: PF00412, PF00595, PF15936

UniProt features (30 total): strand 6, sequence conflict 5, sequence variant 4, modified residue 4, helix 3, domain 2, compositionally biased region 2, chain 1, splice variant 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2V1W	X-RAY DIFFRACTION	1.9
4Q2O	X-RAY DIFFRACTION	2.1
2EEG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50479-F1	70.79	0.35

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 112, 116, 120, 135

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 284 (showing top): RNGTGGGC_UNKNOWN, MODULE_52, ENK_UV_RESPONSE_KERATINOCYTE_UP, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, TAL1ALPHAE47_01, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING, MODULE_118, SRF_C, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, BLALOCK_ALZHEIMERS_DISEASE_UP, GROSS_HYPOXIA_VIA_ELK3_DN, GROSS_HYPOXIA_VIA_HIF1A_DN, GATA1_01, GOBP_SYNAPTIC_SIGNALING

GO Biological Process (4): heart development (GO:0007507), actin cytoskeleton organization (GO:0030036), muscle structure development (GO:0061061), excitatory chemical synaptic transmission (GO:0098976)

GO Molecular Function (7): actin binding (GO:0003779), protein phosphatase binding (GO:0019903), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), muscle alpha-actinin binding (GO:0051371), alpha-actinin binding (GO:0051393), protein binding (GO:0005515)

GO Cellular Component (24): stress fiber (GO:0001725), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), adherens junction (GO:0005912), actin cytoskeleton (GO:0015629), Z disc (GO:0030018), lamellipodium (GO:0030027), early endosome membrane (GO:0031901), early endosome lumen (GO:0031905), filamentous actin (GO:0031941), recycling endosome lumen (GO:0034777), dendritic spine (GO:0043197), postsynaptic membrane (GO:0045211), perinuclear region of cytoplasm (GO:0048471), recycling endosome membrane (GO:0055038), endosome (GO:0005768), endomembrane system (GO:0012505), membrane (GO:0016020), cell projection (GO:0042995), neuron projection (GO:0043005), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	2
early endosome	2
endosome membrane	2
endosome lumen	2
recycling endosome	2
postsynapse	2
animal organ development	1
circulatory system development	1
cytoskeleton organization	1
actin filament-based process	1
anatomical structure development	1
chemical synaptic transmission	1
excitatory postsynaptic potential	1
cytoskeletal protein binding	1
phosphatase binding	1
identical protein binding	1
protein dimerization activity	1
cation binding	1
alpha-actinin binding	1
actinin binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
cell-cell junction	1
cytoskeleton	1
I band	1
cell leading edge	1
plasma membrane bounded cell projection	1
actin filament	1
protein-containing complex	1
dendrite	1
neuron spine	1
synaptic membrane	1
endomembrane system	1

Protein interactions and networks

STRING

946 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDLIM4	ACTN2	P35609	493
PDLIM4	RGMA	Q96B86	477
PDLIM4	GRIA1	P42261	435
PDLIM4	CNN3	Q15417	425
PDLIM4	GAPDH	P00354	421
PDLIM4	ACTN1	P12814	416
PDLIM4	IRF1	P10914	412
PDLIM4	PBXIP1	Q96AQ6	408
PDLIM4	IL2	P01585	396
PDLIM4	MIA2	Q96PC5	396
PDLIM4	SNF8	Q96H20	389
PDLIM4	RSPH1	Q8WYR4	388
PDLIM4	GFAP	P14136	378
PDLIM4	ECRG4	Q9H1Z8	375
PDLIM4	UPK1B	O75841	365
PDLIM4	NUDT14	O95848	365

IntAct

69 interactions, top by confidence:

A	B	Type	Score
ACTN1	PDLIM4	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	PDLIM4	psi-mi:“MI:0915”(physical association)	0.560
AMT	PDLIM4	psi-mi:“MI:0915”(physical association)	0.560
PDLIM4	FAM222B	psi-mi:“MI:0915”(physical association)	0.560
KIR3DL2	METTL15	psi-mi:“MI:0914”(association)	0.530
PDLIM4	E7	psi-mi:“MI:0915”(physical association)	0.490
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
KCNA5	PDLIM4	psi-mi:“MI:0407”(direct interaction)	0.440
PDLIM4	RASSF6	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC4	PDLIM4	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF16	PDLIM4	psi-mi:“MI:0407”(direct interaction)	0.440
ASIC3	PDLIM4	psi-mi:“MI:0407”(direct interaction)	0.440
ATP2B4	PDLIM4	psi-mi:“MI:0407”(direct interaction)	0.440
CYSLTR2	PDLIM4	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	PDLIM4	psi-mi:“MI:0407”(direct interaction)	0.440
DGKZ	PDLIM4	psi-mi:“MI:0407”(direct interaction)	0.440
DOCK4	PDLIM4	psi-mi:“MI:0407”(direct interaction)	0.440
FRMPD4	PDLIM4	psi-mi:“MI:0407”(direct interaction)	0.440
FZD7	PDLIM4	psi-mi:“MI:0407”(direct interaction)	0.440
TAMALIN	PDLIM4	psi-mi:“MI:0407”(direct interaction)	0.440
E6	PDLIM4	psi-mi:“MI:0407”(direct interaction)	0.440
ORF putative E6	PDLIM4	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (50): RBPMS (Two-hybrid), PDLIM4 (Proximity Label-MS), PDLIM4 (Affinity Capture-MS), PDLIM4 (Affinity Capture-MS), PDLIM4 (Proximity Label-MS), PDLIM4 (Proximity Label-MS), PDLIM4 (Proximity Label-MS), PDLIM4 (Two-hybrid), PDLIM4 (Reconstituted Complex), PDLIM4 (Biochemical Activity), PDLIM4 (Two-hybrid), Pdlim4 (Two-hybrid), PDLIM4 (Affinity Capture-Western), PDLIM4 (Affinity Capture-Western), SDCBP (Two-hybrid)

ESM2 similar proteins: A0A1L8F1M4, A8WH69, B1AK53, D3ZQL6, E1BBG2, O43294, O60711, O75112, P36202, P49023, P49024, P50479, P70271, Q09476, Q0VA45, Q2TCH4, Q3MHZ4, Q3SX40, Q3T005, Q3TJD7, Q4V882, Q5R7I1, Q5U464, Q62219, Q62920, Q63618, Q66H76, Q679P3, Q6INU3, Q6P7E4, Q80VP1, Q8BGT6, Q8BYZ1, Q8CI51, Q8K382, Q8N3F8, Q8TDY4, Q8TEH3, Q8VI36, Q91W69

Diamond homologs: A0A1L8F1M4, A0M8R4, A0M8S5, A0M8U6, A1Z6W3, A8WH69, O42565, O43900, P36202, P47226, P50464, P50479, P53667, P53668, P53669, P70271, Q00PK1, Q07DW1, Q07DX3, Q07DY3, Q07DZ4, Q07E27, Q07E40, Q07E51, Q09YI0, Q09YJ2, Q09YK3, Q09YL5, Q09YN8, Q108U9, Q14192, Q174I2, Q17QE2, Q28FG2, Q292U2, Q292U5, Q2IBA3, Q2IBC3, Q2IBH0, Q2LAP6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
transmembrane transport	5	22.8×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

45 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

828 predictions. Top by Δscore:

Variant	Effect	Δscore
5:132271062:A:G	donor_gain	1.0000
5:132271301:AGC:A	acceptor_gain	1.0000
5:132271302:GC:G	acceptor_gain	1.0000
5:132271302:GCG:G	acceptor_gain	1.0000
5:132271302:GCGCT:G	acceptor_gain	1.0000
5:132271462:GGGCG:G	donor_gain	1.0000
5:132271463:GGCG:G	donor_gain	1.0000
5:132271463:GGCGG:G	donor_gain	1.0000
5:132271464:GCG:G	donor_gain	1.0000
5:132271464:GCGG:G	donor_gain	1.0000
5:132271467:G:GG	donor_gain	1.0000
5:132272020:A:AG	acceptor_gain	1.0000
5:132272020:ATCAG:A	acceptor_gain	1.0000
5:132272021:T:G	acceptor_gain	1.0000
5:132272022:CAGG:C	acceptor_loss	1.0000
5:132272023:A:AG	acceptor_gain	1.0000
5:132272023:AG:A	acceptor_gain	1.0000
5:132272023:AGG:A	acceptor_gain	1.0000
5:132272023:AGGG:A	acceptor_gain	1.0000
5:132272024:G:A	acceptor_gain	1.0000
5:132272024:G:GT	acceptor_gain	1.0000
5:132272024:G:T	acceptor_loss	1.0000
5:132272024:GGG:G	acceptor_gain	1.0000
5:132272024:GGGG:G	acceptor_gain	1.0000
5:132272024:GGGGC:G	acceptor_gain	1.0000
5:132257825:CGG:C	donor_gain	0.9900
5:132257825:CGGGT:C	donor_loss	0.9900
5:132257826:GG:G	donor_gain	0.9900
5:132257826:GGG:G	donor_gain	0.9900
5:132257827:GG:G	donor_gain	0.9900

AlphaMissense

2139 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:132257771:T:A	W13R	1.000
5:132257771:T:C	W13R	1.000
5:132257774:G:C	G14R	1.000
5:132257777:T:C	F15L	1.000
5:132257778:T:C	F15S	1.000
5:132257779:C:A	F15L	1.000
5:132257779:C:G	F15L	1.000
5:132257784:T:C	L17P	1.000
5:132257789:G:C	G19R	1.000
5:132257789:G:T	G19C	1.000
5:132257790:G:A	G19D	1.000
5:132257790:G:T	G19V	1.000
5:132257792:G:C	G20R	1.000
5:132257793:G:A	G20D	1.000
5:132257801:T:C	F23L	1.000
5:132257803:C:A	F23L	1.000
5:132257803:C:G	F23L	1.000
5:132257814:T:A	L27H	1.000
5:132257820:T:A	I29N	1.000
5:132262661:T:A	I49N	1.000
5:132262670:T:A	I52N	1.000
5:132262699:C:G	H62D	1.000
5:132262701:C:A	H62Q	1.000
5:132262701:C:G	H62Q	1.000
5:132262708:G:C	A65P	1.000
5:132262712:A:C	Q66P	1.000
5:132262713:G:C	Q66H	1.000
5:132262713:G:T	Q66H	1.000
5:132262721:T:A	I69N	1.000
5:132262721:T:C	I69T	1.000

dbSNP variants (sampled 300 via entrez): RS1000024773 (5:132260914 A>G), RS1000245579 (5:132273875 T>A), RS1000543047 (5:132261215 G>A), RS1000631200 (5:132267155 G>A), RS1000962280 (5:132269648 G>T), RS1001417856 (5:132270620 G>A,T), RS1001606812 (5:132258038 G>A), RS1001700268 (5:132256710 G>A,T), RS1001912279 (5:132268759 T>G), RS1002041529 (5:132264028 T>C), RS1002355821 (5:132261652 C>A), RS1002428128 (5:132261353 G>T), RS1002498173 (5:132259296 C>G,T), RS1002614389 (5:132259462 G>A), RS1002864280 (5:132271966 G>A,C,T)

Disease associations

OMIM: gene MIM:603422 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000939	Osteoporosis

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001438_16	Crohn’s disease	4.000000e-08
GCST001725_83	Inflammatory bowel disease	1.000000e-52
GCST004131_32	Inflammatory bowel disease	4.000000e-27
GCST004132_10	Crohn’s disease	6.000000e-36
GCST004133_36	Ulcerative colitis	2.000000e-06
GCST004863_104	Mosquito bite size	3.000000e-20
GCST006249_92	Serum metabolite levels	2.000000e-11
GCST006585_2263	Blood protein levels	1.000000e-44
GCST007564_20	Asthma or allergic disease (pleiotropy)	5.000000e-10
GCST008163_162	Height	7.000000e-08
GCST008916_106	Asthma	2.000000e-25
GCST010701_41	Cortical surface area (MOSTest)	1.000000e-20
GCST010702_96	Subcortical volume (MOSTest)	2.000000e-08
GCST010703_160	Brain morphology (MOSTest)	3.000000e-09
GCST90000025_12	Appendicular lean mass	1.000000e-42

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008378	mosquito bite reaction size measurement
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	5
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	3
Vorinostat	affects cotreatment, increases expression	2
Cyclosporine	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
bisphenol A	decreases methylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	decreases expression	1
Am 580	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Rosiglitazone	decreases expression	1
Temozolomide	increases expression	1
Decitabine	decreases reaction, increases expression, affects methylation	1
Sunitinib	decreases expression	1
Cadmium	decreases expression	1
Cytarabine	increases expression, decreases reaction	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Furaldehyde	decreases expression, affects cotreatment, affects localization	1
Niclosamide	increases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Sodium Chloride	decreases expression, increases expression, affects cotreatment, affects localization	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.